Biomaterials are being used for the healthcare applications from ancient times. But subsequent evolution has made them more versatile and has increased their utility. Biomaterials have revolutionized the areas like bioengineering and tissue engineering for the development of novel strategies to combat life threatening diseases. Together with biomaterials, stem cell technology is also being used to improve the existing healthcare facilities. These concepts and technologies are being used for the treatment of different diseases like cardiac failure, fractures, deep skin injuries, etc. Introduction of nanomaterials on the other hand is becoming a big hope for a better and an affordable healthcare. Technological advancements are underway for the development of continuous monitoring and regulating glucose levels by the implantation of sensor chips. Lab-on-a-chip technology is expected to modernize the diagnostics and make it more easy and regulated. Other area which can improve the tomorrow’s healthcare is drug delivery. Micro-needles have the potential to overcome the limitations of conventional needles and are being studied for the delivery of drugs at different location in human body. There is a huge advancement in the area of scaffold fabrication which has improved the potentiality of tissue engineering. Most emerging scaffolds for tissue engineering are hydrogels and cryogels. Dynamic hydrogels have huge application in tissue engineering and drug delivery. Furthermore...
A conference, “Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,” was held July 25 to 28, 2011 at the University of Vermont to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.
Halobacterium sp. NRC-1 is a wild-type extremophilic
microbe that is naturally tolerant to high levels of ionizing radiation. Mutants
of strain NRC-1 with even higher levels of resistance to ionizing radiation,
named RAD, were previously isolated after selecting survival to extremely
high-doses of ionizing radiation. These RAD mutants displayed higher
transcription levels for the rfa3 operon, coding two subunits
of the RPA-like putative single-stranded binding protein, rfa3
and rfa8, and a third downstream gene, ral. In
order to bioengineer cells with increased tolerance to ionizing radiation and
further explore the genetic basis of the RAD phenotype, we placed the
rfa3 operon under control of the gvpA
promoter in a Halobacterium expression plasmid, pDRK1. When
pDRK1 was introduced into the wild-type NRC-1 strain, overproduction of the Rfa3
and Rfa8 proteins was observed by Western blotting and proteomic analysis. The
Halobacterium strains expressing Rfa3 and Rfa8 also
displayed improved survival after exposure to ionizing radiation, similar to the
RAD mutants, when compared to wild-type strain NRC-1. The Rfa3 and Rfa8 proteins
co-purified by affinity chromatography on single-stranded DNA-cellulose columns,
confirming the ability of the proteins to bind to single-stranded DNA as well as
their relative abundance in the wild-type...
Significant achievements in the organ replacement approach for malignancies over the last 2 decades opened new horizons, and the age of “Transplant Oncology” has dawned. The indications of liver transplantation for malignancies have been carefully expanded by a strict patient selection to assure comparable outcomes with non-malignant diseases. Currently, the Milan criteria, gold standard for hepatocellular carcinoma, are being challenged by high-volume centers worldwide. Neoadjuvant chemoradiation therapy and liver transplantation for unresectable hilar cholangiocarcinoma has been successful in specialized institutions. For other primary and metastatic liver tumors, clinical evidence to establish standardized criteria is lacking. Intestinal and multivisceral transplantation is an option for low-grade neoplasms deemed unresectable by conventional surgery. However, the procedure itself is in the adolescent stage. Solid organ transplantation for malignancies inevitably suffers from “triple distress,” i.e., oncological, immunological, and technical. Organ bioengineering and regenerative medicine should serve as the “triple threat” therapy and revolutionize “Transplant Oncology.”
Liver bioengineering has been a field of intense research and popular excitement in the past decades. It experiences great interest since the introduction of whole liver acellular scaffolds generated by perfusion decellularization1–3. Nevertheless, the different strategies developed so far have failed to generate hepatic tissue in vitro bioequivalent to native liver tissue. Even notable novel strategies that rely on iPSC-derived liver progenitor cells potential to self-organize in association with endothelial cells in hepatic organoids are lacking critical components of the native tissue (e.g., bile ducts, functional vascular network, hepatic microarchitecture, etc)4. Hence, it is vital to understand the strengths and short comes of our current strategies in this quest to re-create liver organogenesis in vitro. To shed some light into these issues, this review describes the different actors that play crucial roles in liver organogenesis and highlights the steps still missing to successfully generate whole livers and hepatic organoids in vitro for multiple applications.
The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes.
A major challenge in stem cell-based bioengineering of an implantable human tooth is to identify appropriate sources of postnatal stem cells that are odontogenic competent as the epithelial component due to the lack of enamel epithelial cells in adult teeth. In a recent issue (2013, 2:6) of Cell Regeneration, Cai and colleagues reported that epithelial sheets derived from human induced pluripotent stem cells (iPSCs) can functionally substitute for tooth germ epithelium to regenerate tooth-like structures, providing an appealing stem cell source for future human tooth regeneration.
Adeno associated vectors (AAV) have shown considerable promise to treat various genetic disorders in both preclinical and clinical settings mainly because of its safety profile. However, efficient use of AAV to deliver genes in immune-competent sites like muscles and liver requires very high doses which are associated with concomitant cellular immune response against the viral capsids leading to destruction of the transduced cells. Coupled with that, there are enough evidences that at high doses, AAV particles are subjected to increased cellular phosphorylation/uniquitination leading to proteasome mediated degradation and loss of the viral particles. The presence of preexisting immunity against AAV further adds on to the problem which is acting as a major roadblock to efficiently use it as a gene therapy vector in the clinics. To overcome this, rational bioengineering of AAV capsid becomes a prime tool by which specific amino acid residue(s) can be suitably modified/replaced by compatible residue(s) to create vectors having lower host immune response and higher intracellular trafficking rate. This article reviews the various aspects of rationally designing AAV capsids like by site-directed mutagenesis, directed evolution and combinatorial libraries which can create vectors having not only immune evasive property but also enhanced gene expression and transduction capability. One or more combinations of these strategies have strong potential to create novel vectors which will have suitable clinical efficiency even at a low dose.
Non-invasive bioengineering technologies continuously discovered and developed in recent decades provide a significant input to research development and remarkably contribute to the improvement of medical education and care to our patients.
OpenCMISS is an open-source modeling environment aimed, in particular, at the solution of bioengineering problems. OpenCMISS consists of two main parts: a computational library (OpenCMISS-Iron) and a field manipulation and visualization library (OpenCMISS-Zinc). OpenCMISS is designed for the solution of coupled multi-scale, multi-physics problems in a general-purpose parallel environment. CellML is an XML format designed to encode biophysically based systems of ordinary differential equations and both linear and non-linear algebraic equations. A primary design goal of CellML is to allow mathematical models to be encoded in a modular and reusable format to aid reproducibility and interoperability of modeling studies. In OpenCMISS, we make use of CellML models to enable users to configure various aspects of their multi-scale physiological models. This avoids the need for users to be familiar with the OpenCMISS internal code in order to perform customized computational experiments. Examples of this are: cellular electrophysiology models embedded in tissue electrical propagation models; material constitutive relationships for mechanical growth and deformation simulations; time-varying boundary conditions for various problem domains; and fluid constitutive relationships and lumped-parameter models. In this paper...
Microcomputed tomography (microCT) has become a standard and essential tool for quantifying structure-function relationships, disease progression, and regeneration in preclinical models and has facilitated numerous scientific and bioengineering advancements over the past 30 years. In this article, we recount the early events that led to the initial development of microCT and review microCT approaches for quantitative evaluation of bone, cartilage, and cardiovascular structures, with applications in fundamental structure-function analysis, disease, tissue engineering, and numerical modeling. Finally, we address several next-generation approaches under active investigation to improve spatial resolution, acquisition time, tissue contrast, radiation dose, and functional and molecular information.
Endogenous molecular and cellular mediators modulate tissue repair and regeneration. We have recently described antibody mediated osseous regeneration (AMOR) as a novel strategy for bioengineering bone in rat calvarial defect. This entails application of anti-BMP-2 antibodies capable of in vivo capturing of endogenous osteogenic BMPs (BMP-2, BMP-4, and BMP-7). The present study sought to investigate the feasibility of AMOR in other animal models. To that end, we examined the efficacy of a panel of anti-BMP-2 monoclonal antibodies (mAbs) and a polyclonal Ab immobilized on absorbable collagen sponge (ACS) to mediate bone regeneration within rabbit calvarial critical size defects. After 6 weeks, de novo bone formation was demonstrated by micro-CT imaging, histology, and histomorphometric analysis. Only certain anti-BMP-2 mAb clones mediated significant in vivo bone regeneration, suggesting that the epitopes with which anti-BMP-2 mAbs react are critical to AMOR. Increased localization of BMP-2 protein and expression of osteocalcin were observed within defects, suggesting accumulation of endogenous BMP-2 and/or increased de novo expression of BMP-2 protein within sites undergoing bone repair by AMOR. Considering the ultimate objective of translation of this therapeutic strategy in humans...
Cells navigate in response to inhomogeneous distributions of extracellular guidance cues. The cellular and molecular mechanisms underlying migration in response to gradients of chemical cues have been investigated for over a century. Following the introduction of micropipettes and more recently microfluidics for gradient generation, much attention and effort was devoted to study cellular chemotaxis, which is defined as guidance by gradients of chemical cues in solution. Haptotaxis, directional migration in response to gradients of substrate-bound cues, has received comparatively less attention; however, it is increasingly clear that in vivo many physiologically relevant guidance proteins – including many secreted cues – are bound to cellular surfaces or incorporated into extracellular matrix and likely function via a haptotactic mechanism. Here, we review the history of haptotaxis. We examine the importance of the reference surface, the surface in contact with the cell that is not covered by the cue, which forms a gradient opposing the gradient of the protein cue and must be considered in experimental designs and interpretation of results. We review and compare microfluidics, contact printing, light patterning, and 3D fabrication to pattern substrate-bound protein gradients in vitro. The range of methods to create substrate-bound gradients discussed herein makes possible systematic analyses of haptotactic mechanisms. Furthermore...
One challenge faced by stem cell biologists is the bioengineering of an
organ. Ehama et al. (2007, this issue) used cells derived from human and rodent epidermis and
dermal papilla to reconstitute hair-follicle mini-organs. Some result in hair
follicles; others are hair follicle–like. The challenge calls for the
development of a set of criteria to define a hair follicle so that bioengineered
products in the future can be evaluated.
RNA research and therapy relies primarily on synthetic RNAs. We employed recombinant RNA technology toward large-scale production of pre-miRNA agents in bacteria, but found the majority of target RNAs were not or negligibly expressed. We thus developed a novel strategy to achieve consistent high-yield biosynthesis of chimeric RNAs carrying various small RNAs (e.g. miRNAs, siRNAs and RNA aptamers), which was based upon an optimal noncoding RNA scaffold (OnRS) derived from tRNA fusion pre-miR-34a (tRNA/mir-34a). Multi-milligrams of chimeric RNAs (e.g. OnRS/miR-124, OnRS/GFP-siRNA, OnRS/Neg (scrambled RNA) and OnRS/MGA (malachite green aptamer)) were readily obtained from 1 l bacterial culture. Deep sequencing analyses revealed that mature miR-124 and target GFP-siRNA were selectively released from chimeric RNAs in human cells. Consequently, OnRS/miR-124 was active in suppressing miR-124 target gene expression and controlling cellular processes, and OnRS/GFP-siRNA was effective in knocking down GFP mRNA levels and fluorescent intensity in ES-2/GFP cells and GFP-transgenic mice. Furthermore, the OnRS/MGA sensor offered a specific strong fluorescence upon binding MG, which was utilized as label-free substrate to accurately determine serum RNase activities in pancreatic cancer patients. These results demonstrate that OnRS-based bioengineering is a common...
Traumatic brain injury (TBI) affects 5.3 million Americans annually. Despite the many long-term deficits associated with TBI, there currently are no clinically available therapies that directly address the underlying pathologies contributing to these deficits. Preclinical studies have investigated various therapeutic approaches for TBI: two such approaches are stem cell transplantation and delivery of bioactive factors to mitigate the biochemical insult affiliated with TBI. However, success with either of these approaches has been limited largely due to the complexity of the injury microenvironment. As such, this review outlines the many factors of the injury microenvironment that mediate endogenous neural regeneration after TBI and the corresponding bioengineering approaches that harness these inherent signaling mechanisms to further amplify regenerative efforts.
Irreversible end-stage organ failure represents one of the leading causes of death, and organ transplantation is currently the only curative solution. Donor organ shortage and adverse effects of immunosuppressive regimens are the major limiting factors for this definitive practice. Recent developments in bioengineering and regenerative medicine could provide a solid base for the future creation of implantable, bioengineered organs. Whole-organ detergent-perfusion protocols permit clinicians to gently remove all the cells and at the same time preserve the natural three-dimensional framework of the native organ. Several decellularized organs, including liver, kidney, and pancreas, have been created as a platform for further successful seeding. These scaffolds are composed of organ-specific extracellular matrix that contains growth factors important for cellular growth and function. Macro- and microvascular tree is entirely maintained and can be incorporated in the recipient’s vascular system after the implant. This review will emphasize recent achievements in the whole-organ scaffolds and at the same time underline complications that the scientific community has to resolve before reaching a functional bioengineered organ.
Este trabalho foi desenvolvido na estação experimental da Fazenda do Glória, em Uberlândia- MG. O objetivo foi avaliar o uso de formas alternativas, de baixo custo, para a recuperação de voçorocas com revegetação e barreiras vegetais. Voçoroca é o estágio mais avançado dos processos de erosão e a sua recuperação é um desafio, principalmente na condição de lençol aflorado. As pesquisas foram divididas em cinco ensaios objetivando: 1. Monitorar e determinar o percentual de umidade no solo dentro do canal. 2. Avaliar o comportamento da Gliricidia sepium, cultivada em dois ambientes: dentro de voçoroca com lençol aflorado e fora da voçoroca em condições de cerrado. 3. Avaliar o comportamento de Gliricidia sepium, plantada diretamente no campo a partir de estacas, dentro de uma voçoroca, tendo como variável o substrato. 4. Avaliar o estabelecimento de espécies arbóreas nativas (Cytharexyllum myrianthum, Erythrina mulungu, Cróton floribundus e Inga uruguensis), no interior de uma voçoroca, em comparação com a espécie exótica (Gliricidia sepium). 5. Avaliar o monitoramento para barreiras estabelecidas com o uso da bioengenharia e Gliricidia sepium, o estabelecimento das mudas e a contribuição da barreira no período de uma estação chuvosa. Foram realizadas análises físico-químicas do solo dentro do canal e na área de cerrado. O acompanhamento das espécies foi realizado com avaliações fitométricas mensais (altura da planta...
Given the great world energy demand and the environmental costs associated
to fossil fuels use, it is imperative to find a CO2 neutral, sustainable, and
renewable energy source. Microalgae are one of the most studied biofuel
feedstock, mainly because they produce considerable amounts of energetic
compounds (TAG and starch) and other valuable secondary metabolites (such
as pigments, vitamins, and bioplastic). Currently, a two-phase cultivation
strategy including a stress imposition step is used to accumulate interesting
compounds for biofuel production. However, microalgae cell growth is often
reduced, requiring longer cultivation times, and stress imposition techniques
are still expensive, which represent high costs for the microalgal biofuel
production process. In order to make it profitable, a biorefinery approach must
be used, combining the extraction of energetic molecules and high value-added
by-products. However, biomass supply continues to represent a major limiting
factor. To overcome this limitation, the study of the metabolic and regulatory
networks involved in stress response is essential so that potential targets for
bioengineering can be identified. This would allow either the maintenance of
cell growth under stress conditions or the mimicking of a stress condition by
coupling a gene of interest to a promoter induced by a simple stimulus...
Many students in bioengineering and medical physics doctoral programs plan careers in translational research. However, while such students generally have strong quantitative abilities, they often lack experience with the culture, communication norms, and practice of bedside medicine. This may limit students' ability to function as members of multidisciplinary translational research teams. To improve students' preparation for careers in cancer translational research, we developed and implemented a mentoring program that is integrated with students' doctoral studies and aims to promote competency in communication, biomedical ethics, teamwork, altruism, multiculturalism, and accountability. Throughout the program, patient-centered approaches and professional competencies are presented as foundational to optimal clinical care and integral to translational research. Mentoring is conducted by senior biomedical faculty and administrators and includes didactic teaching, online learning, laboratory mini-courses, clinical practicums, and multidisciplinary patient planning conferences (year 1); student development and facilitation of problem-based patient cases (year 2); and individualized mentoring based on research problems and progress toward degree completion (years 3-5). Each phase includes formative and summative evaluations. Nineteen students entered the program from 2009 through 2011. On periodic anonymous surveys...